Rationale: Ghrelin has been shown to mediate food and drug reward in rats and mice, and the rewarding properties of sweet foods and alcohol are known to contribute to overconsumption of these substances. Objective: To investigate the effects of GHS-R1A antagonism in a novel animal model of high alcohol consumption, the prairie vole, and to characterize the role of ghrelin in limited access consumption of a drug (alcohol) and non-drug (sucrose) reward. Methods: Female prairie voles were given four 2-h two-bottle drinking sessions, occurring every other day. During drinking sessions, animals had access to 20% ethanol vs water or 10% sucrose vs water. Pre-treatment with the GHS-R1A antagonist JMV 2959 (i.p.; 0.0, 9.0 mg/kg Experiments 1 and 2;0.0, 9.0, 12.0 mg/kg Experiments 3 and 4.) occurred 30-min before the fourth session. To determine if the amount of exposure to sucrose sessions affected the efficacy of JMV 2959, in Experiment 5 animals were given 16 daily 2-hr drinking sessions with 10% sucrose vs water. JMV 2959 treatment (0.0 or 9.0 mg/kg) occurred 30-min prior to the 16th session. Results: JMV 2959 reduced alcohol but not sucrose preference. Even after extended experience with sucrose sessions, JMV 2959 had no effect on sucrose preference or consumption. Conclusion: These findings demonstrate that GHS-R1A antagonism reduces alcohol preference, but suggest limitations on the role of ghrelin in the preference for and consumption of naturally rewarding substances. (C) 2015 Elsevier Inc. All rights reserved.

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